Monomers of human beta 1 beta 1 alcohol dehydrogenase exhibit activity that differs from the dimer

A previously unreported enzymatic activity is described for monomers of the beta 1 beta 1 isoenzyme of human alcohol dehydrogenase that were prepared from dimeric enzyme by freeze-thaw in liquid nitrogen. Whereas the dimeric enzyme has optimal activity at low substrate concentrations (2.5 mM ethanol, 50 microM NAD+; "low Km" activity), the monomer has its highest activity at high substrate concentrations (1.5 M ethanol, 2.5 mM NAD+; "high Km" activity). While the activity of the monomer does not appear to be saturated at 1.5 M ethanol, its maximal activity at this high ethanol concentration exceeds the Vmax of the dimer by about 3-fold. The apparent Km of NAD+ with monomers is 270 microM, and no activity could be detected with nicotinamide mononucleotide as cofactor. During gel filtration the high Km activity elutes at a lower apparent molecular weight position than the dimer. The kinetics of monomer-to-dimer reassociation are consistent with a second-order process with a rate constant of 240 M-1 s-1. The reassociation rate is markedly enhanced by the presence of NAD+. During refolding of beta 1 beta 1 following denaturation in 6 M guanidine hydrochloride, an enzyme species with high Km activity and spectral properties similar to the freeze-thaw monomer is observed, indicating that a catalytically active monomer is an intermediate in the refolding pathway. The enzymatic activity of the monomer implies that the intersubunit contacts of beta 1 beta 1 are not crucial in establishing a catalytically competent enzyme. However, the differences in specific activity and Km between monomer and dimer suggest that dimerization may serve to modulate the catalytic properties.     

Issues and controversies in venous thromboembolism

The developmental expression of salivary glycoconjugates was investigated in the rat submandibular and sublingual glands by conventional and lectin histochemistry. By the time of the first differentiation of secretory structures, in spite of similar morphological features, a different histochemical reactivity was detected, accounting for a relevant content of neutral glycoconjugates in the submandibular gland and the occurrence of both neutral and acidic glycoconjugates in the sublingual one. The use of lectins allowed the main changes of secretory components to be noted around gestational day 18. DBA and WGA lectins seemed to act as pre- and post-natal development markers while Con A lectin was indicative of post-natal differentiation. Taken together, data from lectin histochemistry indicated the transitional occurrence of glycoconjugates, probably involved in temporally restricted functions, as well as the co-existence of different secretory components that might also reflect maturational changes of single products.     

Asymmetrical hemispheric activation and emotion: the effects of unilateral forced nostril breathing

Relative nostril efficiency is associated with greater activation of the hemisphere contralateral to the more efficient (dominant) nostril and with improved performance on cognitive tasks which reflect the functions of that hemisphere (see Shannahoff-Khalsa, 1993, for review). In this experiment we demonstrate a similar relationship between nasal efficiency and the emotional functions of the cerebral hemispheres. Following left nostril forced breathing through the dominant nostril, subjects report a more negative emotional state, score higher on the Spielberger State Anxiety Inventory, and tell stories about an ambiguous picture that are more negative in emotional tone. These results are similar to those found with unilateral muscle contractions and therefore support the hypothesis that unilateral contractions are effective because of contralateral hemispheric activation.     

Swallow recovery in an oral cancer patient following surgery, radiotherapy, and hyperthermia

BACKGROUND: No study has examined the nature and extent of swallowing impairment in oral cancer patients following treatment with combined hyperthermia and interstitial radiotherapy. Few studies have examined the effects of voluntary swallow maneuvers (supersupraglottic and Mendelsohn) on pharyngeal phase swallowing in the oral cancer patient treated with surgery or radiotherapy. This study examined the effects of combined radiotherapeutic salvage treatments of hyperthermia and interstitial implantation and swallow recovery using swallow maneuvers in a surgically treated and irradiated oral cancer patient. METHODS: The patient under study, a 51-year-old man, underwent radiotherapy, according to Radiation Therapy Oncology Group (RTOG) protocol #8419, consisting of a combination of interstitial irradiation and hyperthermia to the base of tongue, for a recurrent squamous cell cancer. He underwent videofluorographic (VFG) examination of his swallowing, a modified barium swallow at three time points: 2 days following radiotherapy treatment (VFG1), 4 weeks later (VFG2), and 8 months later (VFG3). Temporal and biomechanical analyses of swallows were performed at each time point. RESULTS: Swallow maneuvers and time resulted in improved laryngeal elevation and laryngeal vestibule closure during the swallows on VFG2. Maximum upper esophageal sphincter (UES) opening width and duration were more normal. Fewer swallows were required for bolus clearance through the pharynx. Base of tongue tissue necrosis occurred as a complication of radiotherapy between VFG2 and VFG3, with resultant severe reduction in posterior movement of the tongue base, incomplete tongue base contact to the posterior pharyngeal wall, reduced laryngeal elevation, and incomplete laryngeal vestibule closure during swallowing at VFG3. UES opening became less normal and a greater number of swallows were required for bolus clearance through the pharynx. CONCLUSIONS: Combined interstitial irradiation and hyperthermia can cause oropharyngeal swallowing problems. Time and swallow therapy can improve these swallow disorders. Tongue base tissue necrosis can cause further swallow impairment, emphasizing the importance of the tongue base in normal deglutition. Further studies are needed to examine the impact of combined hyperthermia and interstitial implantation for treatment of tongue base tumors on swallow functioning in a larger group of patients.     

Adenosine A1 receptors mediate hypoxia-induced inhibition of electrically evoked transmitter release from rat striatal slices

We have examined the role of adenosine in mediating effects of mild hypoxia on electrically evoked transmitter release. Rat striatal slices, preincubated with [3H]dopamine and [14C]choline, were superfused continuously and stimulated electrically. Before and during the second stimulation, some slices were superfused with Krebs' solution with lowered oxygen. This mild hypoxia caused a significant increase of the electrically evoked outflow of endogenous adenosine, hypoxanthine and inosine into the superfusion buffer, whereas electrically evoked release of [3H]dopamine and [14C]acetylcholine was significantly decreased. The addition of 8-cyclopentyl-1,3-dipropylxanthine, a selective adenosine A1 receptor antagonist, blocked the hypoxia-induced inhibitory effect on the evoked release of these two transmitters in a concentration-dependent manner. In summary, the results show that reduction of the oxygen supply to striatal slices results in an increased release of endogenous adenosine, which, by acting on adenosine A1 receptors, decreases the electrically evoked release of dopamine and acetylcholine.     

Abnormal neurological findings at first admission in patients with schizophrenia or schizophreniform disorders. Results of computer tomography and measurement of regional cerebral blood flow

Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT and regional cerebral blood flow as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.     

Physician-assisted suicide and older patients'' perceived duty to die

The Lambert-Eaton syndrome is an autoimmune disease affecting the presynapse of the neuromuscular junction. Proximal muscle fatigue of the limbs is improved by repeated maximal voluntary contractions. Generally, patients present hypo or areflexia and frequently a dry mouth syndrome. In 50% of the cases, the Lambert-Eaton syndrome is associated with small-cell bronchogenic carcinoma. The different treatments proposed in the literature for Lambert-Eaton paraneoplastic syndrome focus on treatment of the primary tumor. Symptomatic treatment of the junctional disorder are based on cholinergic drugs, immunosuppression and immunomodulation, useful in case of unsuccessful antineoplastic therapy.